Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.
Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.
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DOI：
10.1055/s-0038-1641755
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发表时间：
2018-06
影响因子：
6.7
通讯作者：
von Drygalski A
中科院分区：
文献类型：
--
作者：
Cooke EJ;Zhou JY;Wyseure T;Joshi S;Bhat V;Durden DL;Mosnier LO;von Drygalski A
血管重构是血友病性关节病（HA）的一个突出特征，可能是再出血的基础，但血管改变的性质和潜在机制在很大程度上仍然未知。在这里，我们的目的是表征关节血肿后滑膜血管重塑和血管完整性，以及炎症和组织修复途径的时间变化。采用功率多普勒（MSKUS/PD）肌肉骨骼超声对30例血友病（PWH）患者急性疼痛关节进行影像学检查，观察血管异常和积血情况。在PWH患者中，30例疼痛的关节发作中有19例与关节出血有关，血管灌注异常是出血关节所特有的。采用fⅷ缺陷小鼠诱导性关节出血模型，分别用MSKUS/PD和白蛋白外渗法对血管重构（α-平滑肌肌动蛋白（αSMA）表达）和体内血管灌注和通透性进行组织学评估。通过实时聚合酶链反应对小鼠滑膜中炎性（M1）和修复性（M2）巨噬细胞标志物进行定量。在fviii缺陷小鼠诱导血关节后，PWH中观察到的血管灌注异常重现。在fviii缺陷小鼠出血后2周，炎症巨噬细胞M1标记物短暂升高后，新生血管和血管通透性明显增加。这些血管变化在第4周消退，而血管重构，通过结构变化和明显的αSMA表达来证明，伴随着修复性巨噬细胞M2反应持续存在。总之，关节血肿导致伴随新生血管和相关血管通透性的短暂炎症，而随后的组织修复机制与血管重构相吻合。总之，这些血管变化可能促进再出血和血凝素进展。
Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterise synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in FVIII-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin (αSMA) expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10 week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularisation and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression.
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影响因子：
5.9
作者：
Bonnefoy, Olivier;Diris, Benoit;Hauger, Olivier
通讯作者：
Hauger, Olivier
影响因子：
6.7
作者：
Martinoli, Carlo;Alberighi, Ornella Della Casa;Morfini, Massimo
通讯作者：
Morfini, Massimo
影响因子：
3.9
作者：
Aznar, J. A.;Lucia, F.;Cortina, V. R.
通讯作者：
Cortina, V. R.
影响因子：
3.9
作者：
Hua, B.;Olsen, E. H. N.;Manon-Jensen, T.
通讯作者：
Manon-Jensen, T.
影响因子：
3.9
作者：
Hakobyan, N;Kazarian, T;Valentino, LA
通讯作者：
Valentino, LA